Otitis media with effusion (OME), or serous otitis media, is a common condition in children and frequently leads to a moderate deafness at a critical age of development. The long-term objectives of this study are: 1) to determine the pathogenesis of OME in humans, 2) to develop suitable animal models for OME, and 3) to develop a scientific rationale for diagnostic, preventive and management strategies for OME. The specific objectives are to define the roles of tubal dysfunction, antecedent acute bacterial otitis media, respiratory virus, bacterial (or viral) antigens, bacteria- (or virus-) host interaction, immune protection, immune injury, and antibiotics in the pathogenesis of OME, using microbiological, immunochemical, histopathological and immunocytochemical techniques in human OME patients and in animal experimental models. The major hypotheses to test are: 1. Initial infection may be modified by the local production of bacteriostatic substances (immunoglobulins and lysozyme), impaired phagocytic function, and/or inadequate antibiotic treatment, leading to OME. 2. After initial infection, dead bacteria or bacterial (or viral) antigens may remain in the middle ear due to poor tubal function, which can elicit immune injury or nonspecific activation of mediators of inflammation, leading to OME. Such substances include endotoxin and peptidoglycan. 3. Viral infection (upper respiratory tract) may predispose the middle ear to bacterial infection due to suppression of immune responses and/or impairment of local clearance mechanisms. 4. Early antibiotic treatment of an initial ear infection prevents the development of adequate immunity of the ear, particularly in the young age group (under two years of age) whose immune systems are being developed, and subsequent infection results in OME due to the incomplete development of immunity in the middle ear.